Animals experimentally infected with SIV experience a transitory panleukopenia followed by a lymphocytic leukosytosis. Recently, we demonstrated that the chemokine receptors CCR5 and CXCR3, which are expressed on activated human lymphocytes, may be involved in cell trafficking to peripheral tissues. Coincidentally, CCR5 is a major co-receptor for macrophage-tropic strains of HIV-1 and a variety of SIV isolates. To determine if CCR5 and CXCR3 are involved in lymphocyte trafficking to the lymph node during acute SIV infection, we infected two groups of rhesus monkeys with equal doses of the cloned viruses SIVmac239 (T cell tropic) and SIVmac239/316 (macrophage tropic). Peripheral blood and lymph node lymphocyte expression of CD3, CD4, CD8, CCR5 and CXCR3 were monitored periodically by two color flow cytometric analysis. Following infection, the percentage of peripheral blood CD4+CCR5+, CD8+CCR5+, CD4+CXCR3+ and CD8+CXCR3+ lymphocytes decreased in parallel until day 7 (n+3) or day 14 (n=1) at which time preferential expansion of CD8+CCR5+ and CD8+CXCR3+ lymphocytes began. SIVmac239/316-infected animals had a greater peak number of CCR5+ and CXCR3+ peripheral blood lymphocytes than SIVmac239-infected animals, suggesting a more vigorous immune response to the macrophage tropic virus. Changes in lymph node CCR5+ and CXCR3+ lymphocytes mirrored changes in the blood, suggesting that there was no preferential trafficking of these cell populations to the lymph node.